Cancer is a leading cause of death that significantly affects the life expectancy of every nation. Colorectal cancer (CRC) is the third most commonly diagnosed and second most deadly cancer globally (WHO, 2021) that accounting for approximately 9.39% of death of all recorded cancers in 2020 (Ferlay et al., 2020; Hossain et al., 2022). CRC incidence is expected to double by 2035 worldwide due to the fast acceleration of diagnosed cases in the elderly. Less developed countries are expected to rise in diagnosed cases of CRC (Papamichael et al., 2015; Hossain et al., 2022).

The term CRC is specific to the large intestine and rectum, where it develops from the abnormal growth of glandular epithelial cells. This development occurs when epithelial cells acquire a succession of genetic or epigenetic alterations that provide them with a selective advantage of hyper-proliferation (Testa et al., 2018). These out of control growing cells produce a benign adenoma, which then progresses to carcinoma and metastasis by three major pathways: microsatellite instability (MSI), chromosomal instability (CIN), and CpG island methylator phenotype (CIMP) (Vogelstein et al., 1988; Nguyen and Duong, 2018; Malki et al., 2020). Like any other tumour or cancer, CRC is classified into stages: Stage 0 (carcinoma in situ) to stage IV. Standard treatment options for the stages 0 –II CRC are surgery, whereas stage III requires surgery and adjuvant chemotherapy, and stage IV and recurrence CRC involve surgery, chemotherapy, and targeted therapy (PDQ, 2021).

Regular screening can prevent CRC. As a polyp takes 10–15 years to be cancerous, detecting and removing polyps at an early stage is critical. However, only 40% of CRC are found at early stages, and sometimes CRC recurs after treatment (ACS, 2020). For CRC treatment strategy, Food and Drug Administration (FDA) approved at least 30 different drugs (Supplementary Table S1), and either singly or in combination with other drugs (Supplementary Table S2) are used for CRC treatment. These chemotherapeutic drugs are exposed to the cancer cells and simultaneously damage healthy cells. Consequently, these drugs manifest several adverse effects, including fatigue, headache, muscle pain, stomach pain, diarrhoea and vomiting, sore throat, blood abnormalities, constipation, neuronal damage, skin changes, memory problems, loss of appetite, and hair loss (ACS, 2020).

Even though the overall survival of individuals with advanced CRC has increased in recent decades due to new chemotherapy regimens (Supplementary Tables S1, S2); however, in nearly all patients with CRC, current systemic chemotherapies developed resistance (Cho and Hu, 2020), limiting the therapeutic efficacy of anti-cancer medicines and ultimately leading to chemotherapy failure. Chemotherapeutic drug resistance is a major issue in CRC treatment in the current clinical practice. Apart from this limitation, the access to diagnosis and treatment of CRC for survival is less accessible in developing countries, particularly for rural people, where about 44% of the world’s people currently live (World Bank, 2021). Therefore, nearly half the world’s population lacks the means to diagnose and treat.

According to World Health Organization (WHO), 75–80% of the world’s population solely rely on traditional medical systems for their first line of treatment due to concerns about the safety and efficacy of synthetic drugs (Hossain et al., 2014; Urbi and Zainuddin, 2015; Hossain and Urbi, 2016; Hossain M. S. et al., 2021). On the contrary, for being comparatively safe, natural products have gained tremendous importance as sources of polypharmacological drugs for infectious diseases, cancers, and neurological disorders (Hossain S. et al., 2021; Farooq et al., 2021). Moreover, indications of the importance of plants for diverse ailments in religious scripts attracted more researchers focusing on evaluating the scientific validity of traditional claims (Hossain et al., 2014; Hossain, 2016; Hossain et al., 2016). So, finding safer alternatives to systematic chemotherapeutic drugs from natural sources are an important and worthy study.

Herbs and spices have been commonly used as condiments to enrich aroma, taste, and colour for thousands of years. Even though they are consumed in small amounts, these herbs and spices contain many bioactive compounds and beneficial health effects. The role of spices and herbs in the inhibition of CRC cells growth has been reported in many recent studies (Zheng et al., 2016; Jaksevicius et al., 2017; Aasim et al., 2018; DeLuca et al., 2018; Khor et al., 2018; Wani and Kumar, 2018; Aiello et al., 2019; Rajasekaran, 2019; Buhrmann et al., 2020; Dandawate et al., 2020; Ganesan et al., 2020; Hallajzadeh et al., 2020; Hu et al., 2020; Malmir et al., 2020; Martínez-Aledo et al., 2020;; Pricci et al., 2020; Badsha et al., 2021; Kammath et al., 2021; Karthika et al., 2021). There is increasing evidence of preventing CRC by consuming fruits and vegetables, while red meat enhances the risk factors (Hallajzadeh et al., 2020). Similarly, dietary fibre was contradictory until recent findings showed that high dietary fibre could prevent cancers, including CRC (DeLuca et al., 2018; Masrul and Nindrea, 2019; O'Keefe, 2019). For example, consumption of one to three tablespoons of ground flaxseeds (FS) per day (8–24 g/day) has been suggested as part of a healthy eating pattern that works as a chemotherapeutic agent against CRC development (DeLuca et al., 2018).

Since many disease conditions, including CRC, commonly treated with culinary herbs and spices in traditional medical systems, are considered self-limiting, their purported benefits need critical evaluation intended for CRC management. This would be a worthy study for the community, particularly clinical practitioners and CRC patients. Therefore, in this study, six commonly used herbs and spices: ginger (Zingiber officinale Roscoe), turmeric (Curcuma longa L.), garlic (Allium sativum L.), fenugreek (Trigonella foenum-graecum L.), sesame (Sesamum indicum L.), and flaxseed (Linum usitatissimum L.) were chosen to evaluate their chemoprotective chemotherapeutic roles in CRC management critically and explored the possibility of developing these agents as anti-CRC pharmaceuticals. Scientific evaluation of these plants against cancers, particularly CRC, is increased over the last few years, and turmeric is the most extensively used spice evaluated for CRC (Figure 1).

Initially, this study comprehensively discussed the molecular basis of CRC development, followed by culinary and traditional uses, current scientific research, and publications of selected herbs and spices on cancers and their role in CRC management with underlying molecular mechanisms of action. Lead compounds have been discussed comprehensively for each herb and spice, including anti-CRC phytoconstituents, antioxidant activities, anti-inflammatory properties, and finally, anti-CRC effects with treatment mechanisms. Future possible works have been suggested where applicable.

Reactive oxygen species (ROS) are produced after exposure to different physical agents, including ultraviolet rays and heat, as well as after chemotherapy and radiotherapy in cancer treatment. Over the past few decades, researchers have realized that ROS plays a significant role in the aetiology of various diseases, including cancer, cardiovascular disease, and inflammation injury. Excessive production of ROS in cellular life needs to be regulated tightly. Because ROS have the potential to initiate the degenerative process in cells; however, living organisms have several antioxidant systems that scavenge the adverse effects of ROS on cells (Karker et al., 2016). These drastic impacts on cells include oxidative stress, damaging biomolecules, including DNA, lipid oxidation, protein degradation, and cellular apoptosis (Figure 3) (Valko et al., 2007).

ROS are by-products of regular cellular metabolism that play crucial roles in activating signalling pathways in cellular life (Perillo et al., 2020). When cells or tissues are exposed to prolonged environmental stress, ROS are created over an extended period, resulting in irreversible damage to cell structure and function, as well as the induction of somatic mutations and neoplastic transformation (Khandrika et al., 2009). Indeed, oxidative stress is associated with cancer onset and development, either by increasing DNA mutations or generating DNA damage, genome instability, and cell proliferation (Figure 3) (Fang et al., 2009; Visconti and Grieco, 2009). Additionally, proteins and lipids are also key oxidative targets, and altering these molecules increases the risk of mutagenesis (Schraufstätter et al., 1988). The adverse effects of ROS can be tightly controlled through a sophisticated enzymatic antioxidant system [e.g., superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase, and catalase] (Soraya and Mozafar, 2018).

Chronic inflammation is caused by various biological, pharmacological, and physical factors, and it has been linked to an elevated risk of numerous types of cancer in humans, including CRC. Epidemiological and experimental evidence suggests that oncological illnesses like cancer have been linked to this inflammation (Reuter et al., 2010). This inflammation is now regarded as a “secret killer” for diseases such as cancer. For example, inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis are associated with an increased risk of colon adenocarcinoma, and chronic pancreatitis is related to an increased rate of pancreatic cancer (Reuter et al., 2010).

An elevated ROS is produced in the inflammatory cells due to increased oxygen absorption in the damaged area. As a result of the increased ROS, the latent TGF-complex is activated, which binds to its receptor and activates different signalling pathways, such as SMAD2/3, PI3K, MAPK/AP-1, and JNK. (Coussens and Werb, 2002). In addition, inflammatory cells also generate soluble mediators, such as cytokines and chemokines, which persuade changes in transcription factors and can trigger different signal transduction cascades, including NF-κB, STAT3, and activator protein-1 (AP-1), Nrf2 (Figure 3). The aberrant expression of inflammatory cytokines like TNF, different interleukins (i.e., IL-1, IL-6, IL-10, IL-11, IL-12, IL-22, IL-23), and chemokine IL-8 have also been reported to play a pivotal role in oxidative stress-induced inflammation (Kanda et al., 2017). Therefore, this sustained inflammatory/oxidative stress leads to damage to neighbouring healthy epithelial and stromal cells, and prolonged time may lead to carcinogenesis because of genome instability, activate of the growth-promoting oncogene, alteration of genes that regulate apoptosis, and loss of tumour suppressor genes (Federico et al., 2007; Liu et al., 2021).

The botanical name of ginger is Zingiber officinale Roscoe, which belongs to the family Zingiberaceae. It is a herbaceous perennial flowering plant that originated in Southeast Asia. It is one of the most consumed dietary condiments globally and is now produced worldwide, including in Bangladesh, India, China, Nigeria, Nepal, Indonesia, and Japan (Surh, 1999). The rhizome, the horizontal stem from which the roots grow, is the central portion of ginger that is widely used and consumed in numerous forms, such as fresh, dried, pickled, preserved, crystallized, candied, powdered or ground (Bode and Dong, 2011).

Ginger is an excellent source of antioxidants used to treat ailments from colds to cancer (Bode and Dong, 2011). The popularity of ginger for scientific research has surged in recent years. As of 15 August 2021 (Scopus database), approximately 12,092 papers with a focus on the beneficial effects of ginger have been published between 1853 and 2021. The papers focused on only cancer is 33%, while 7% focused mainly on CRC (Figure 1). This plant has many other health benefits related to cancers (Figure 5).

Turmeric (Curcuma longa L.) is also derived from the Zingiberaceae family. In addition to improving taste, turmeric was one of the spices used to preserve food. Yellow turmeric rhizomes give an aromatic flavor and slightly bitter taste. (Dhakal et al., 2019). Turmeric rhizomes are an excellent antioxidant source, and it has free-radical scavenging properties (Restrepo-Osorio et al., 2020). Its extracts (1–2%) are considered a natural preservative and free from microbial contamination at least for 90 days of storage (Gul and Bakht, 2015). Turmeric is generally given at a dose of 5–500 mg/kg for nutritional purposes depending on the food categories like dairy products, beverages, cereals, mustard, food concentrates, pickles, sausages, confectionery, and ice cream, meat, fish, eggs, and other confectionaries. It is also mixed with other compounds, including annatto, seasonal sauces, mayonnaise, and butter (Sharifi-Rad et al., 2020). Turmeric is rich in polyphenols and universally known as the “wonder drug of life.” The lead compound, curcumin, is responsible for a wide range of pharmacological activities, including antioxidant, anti-cancer, anti-arthritic, anti-microbial, anti-diabetic, anti-inflammatory activities, and avails in the treatment of many ailments, including tendinitis, liver cirrhosis, Alzheimer’s disease, heart attack, hypoglycemia, gastrointestinal problems, worms, swelling, cancer, skin and ocular perceiver infections (Gera et al., 2017). Currently, the major focus has been given by scientists on cancer. As of 15 August 2021 (Scopus database), the effect of turmeric/curcumin on cancer; between 1881 and 2021, was the topic of 11,519 papers, with 53% related to cancer and 16% associated exclusively on CRC (Figure 1). The wide application of curcumin in diverse fields had caused its global market to expand exponentially. The pharmaceutical industry, particularly those focused on anti-cancer medication formulations, is the most significant application category, accounting for more than half of the global market, followed by the food and cosmetic industries (Sharifi-Rad et al., 2020).

Another commonly consumed spice is garlic (Allium sativum L.), a member of the family Liliaceae (Shang et al., 2019). Garlic can be consumed raw or cooked and in powder or oil form. Garlic as traditional medicine has been documented in ancient writings of Egypt, Greece, China, and India as early as 3,000 years ago (Rivlin, 2001; Omar and Al-Wabel, 2010). Garlic has been shown to reduce the incidence of heart disease and cancer in epidemiologic and preclinical investigations, and it has also been claimed to be an anti-cancer dietary component (Bayan et al., 2014). There are around 33 sulfur compounds, including alliin, allicin, ajoene, allyl propyl disulfide, diallyl trisulfide, S-allyl cysteine, vinyldithiines, S-allyl mercapto cysteine, and others, several enzymes (i.e., allinase, peroxidases, myrosinase), 17 amino acids like arginine and others, and minerals, such as selenium, germanium, tellurium and other trace minerals (Newall et al., 1996; Martins et al., 2016; Abe et al., 2020). As of 15 August 2021 (Scopus database), 19,339 papers related to the merits of garlic consumption have been documented between 1854 and 2021. One-third of these published records were related to its benefits in cancer modulation, while 8 % pivoted on its benefits for CRC prevention and management (Figure 1). There is compelling evidence that garlic and related sulfur components can reduce cancer risk and affect the biological behaviour of tumours. A high intake of garlic is associated with decreased risks for stomach and CRC (Omar and Al-Wabel, 2010).

Fenugreek (Trigonella foenum-graecum L.) belongs to the family Leguminosae. It has long been used as a spice to improve the sensory quality of cuisines across the world, including in Bangladesh, India, and Pakistan (Wani and Kumar, 2018; Singh et al., 2020). Its seeds and green leaves, commonly used as leafy vegetables and seasonings, are now widely cultivated for medicinal purposes. They also enhance flavour, colour, and texture in foods (Tewari et al., 2020). Although modern medicine has made incredible advances, the usage of herbal plants for treating or preventing diseases is still widely used due to their diverse nutraceutical capabilities and safety. Among many spice crop plants that are nutritious, functional, and therapeutic, fenugreek is popular with all these characteristics. Recently, it has gained tremendous scientific attention for further evaluation and validation of nutraceutical and health benefits, especially lifestyle-related diseases and cancer. Our systematic investigation in the Scopus database revealed that scientists published around 3,713 papers between 1931 and 2021. Almost a quarter of the articles focused on cancers, and 5% of papers precisely focused only on CRC (Figure 1). The health benefits of fenugreek that lead to anti-cancer effects are summarised in Figure 10.

Sesame (Sesamum indicum) from the Pedaliaceae family is one of the earliest domesticated oilseed crops known to humankind with its multifarious uses. It is mainly consumed in various cuisines and preferably used with bread, biscuits, crackers, and so forth and as a seasoning in food worldwide (Namiki, 2007). Sesame has an essential role in human nutrition due to its rich chemical compositions like oil (44–58%), protein (18–25%), carbohydrates (∼13.5%), minerals and vitamins (Elleuch et al., 2007; Hassan, 2012; Lim, 2012). Sesame seeds have multiple potential bioactive compounds that are beneficial components in food and are accountable for disease-preventing properties. These chemical compounds include phenolics, carotenoids, phytosterols, and polyunsaturated fatty acids, often utilized as antioxidants and for other purposes (Pathak et al., 2017). Recent studies demonstrated that the leaves and shoots of sesame plants are used as vegetables, and the leaves contain valuable nutrients such as amino acids responsible for various traditional uses, including pain relief, catarrh, eye pain, bruises, and erupted skin lesions. In Japan, young sesame leaves (30–70 cm tall, 40–60 days after planting) are dried and sold as a health food supplement (Fuji et al., 2018).

The seeds contain lignans such as sesamin and sesaminol and are highly valued as traditional health and nutraceutical food. Young sesame leaves contain three iridoids (lamalbid, sesamoside and shanzhiside methyl ester) and seven polyphenols (cistanoside F, chlorogenic acid, pedalitin-6-O-laminaribioside, pedaliin, isoacteoside, pedalitin and martynoside), and acteoside. These compounds show potential radical scavenging effects in assays like the DPPH, ABTS, and superoxide anion radicals test (Matsufuji et al., 2011; Fuji et al., 2018). However, sesamin, a major lignan in sesame oil did not show antioxidant in vitro activity (Nakai et al., 2003). Interestingly, on the other hand, this compound showed protective effects against oxidative damage in rat liver. The same metabolites were found as glucuronic acid and/or sulfuric acid conjugates in substantial amounts in rat bile after oral administration of sesamin (Nakai et al., 2003). Therefore, sesamin is considered as a prodrug. On giving 10 mg/kg or 100 mg/kg of sesamin (S10, S100) to 32 male ddY mice 2 h before swimming exercise using a new forced-swimming apparatus, their plasma lipid peroxide level was significantly suppressed, while the level in the control group increased significantly after exercise (p < 0.01). S100 showed significantly higher total GPx activity and GST activity in the liver compared to control (p < 0.05) (Ikeda et al., 2003). This finding suggested that sesamin may enhance liver LPO degradation, resulting in strong protective effects against exercise-induced plasma lipid peroxidation. Sesamin in vivo metabolites with the catechol group is the most efficient antioxidants (Papadopoulos et al., 2016). The highly antioxidative action of sesame oil has been clarified, and it has been determined that recently discovered lignans mediate with tocopherols. A novel synergistic effect of sesame lignans with tocopherols has been found, and it is believed to be responsible for the antiaging effect of sesame. Sesame lignans inhibit metabolic decomposition of tocopherols, which results in the antiaging effect of sesame being attributed to strong vitamin E activity (Namiki, 2007). A systematic search in the Scopus database showed that around 11,089 articles were published between 1898 and 2021. Among these publications, about 15% emphasized cancers, and 2% precisely concentrated on CRC alone (Figure 1).

Flaxseed (Linum usitatissimum L.) from the Linaceae family is one of the world’s oldest cultivated herbaceous crops. It is still widely grown for its oil, fibre, and nutritional value. Flaxseed oil is high in omega-3 fatty acid linolenic acid (55%), an attribute that boosts its role as a functional food. Additionally, flaxseeds are used in animal feed to boost reproductive health (Oomah, 2001; Turner et al., 2014). The flaxseed products include whole seed (ground), flaxseed oil (partially defatted), fully defatted (solvent extraction), mucilage extract, flaxseed hull, oleosomes, and alcohol extract. Each of these products has particular health benefits. Reports typically neglect the presence of many bioactive chemicals in flaxseed fractions or attribute the impact to a single component. However, whole flaxseed is widely accepted as a healthy food with anti-cancer activity (Shim et al., 2014). In female rat mammary glands, flaxseed flour reduces epithelial cell proliferation and nuclear abnormalities that indicate the reduction of mammary tumour growth in the later stages of carcinogenesis (Serraino and Thompson, 1991; Thompson et al., 1996). Recently the growth of cancer research using flaxseeds has increased significantly. Our team’s systematic literature search (Scopus database) revealed that about 7,357 articles were published between 1844 and 2021. About 22% concentrated on cancers among these publications, and 4% was specifically spotlighted on CRC (Figure 1).